Work has continued on the morphogenesis of hypertensive cardiovascular disease. We have completed a morphometric analysis of ventricular hypertrophy in two-kidney Goldblatt hypertension (2-KHH) in the rat. Carotid artery constriction does not protect the ipsilateral cereberovasculature in the rat from the increased premeability associated with severe 2-KGH oracute angiotensin-II (AII) induced hypertension. 2-KGH in the rat produces medial necrosis and hyperplastic lesions in epicardial and intramyocardial arteries. Foci of intramural fibrin accumulation are also noted in intramyocardial arteries. Ragions of subendocardial necrosis are present in the left ventricle. We have observed cardiomegaly, foci of myocardial necrosis and degenerative changes in intramural arteries and perivascular nerves in hearts from genetically diabetic (C57BL/KsJ db/db) mice. In the absence of epicardial arterial disease, these lesions together constitute a diabetic cardiomyopathy. Analysis of cardiac lysosomal enzymes in these animals indicates decrease in the activity of these enzymes, particularly these involved in the metabolism of proteoglycans and membrane constituents (aryl sulphatese, N-acetyl-B-glucosaminidase and B-glucoronidase). Studies will continue on the pathogenesis of AII induced proteinuria and coronary artery necrosis, as well as on the role of lysosomal and non-lysosomal proteases in the development of diabetic cardiomyopathy in the mouse. Endothelium form cerebrovascular resistance vessels of normotensive and 2-KGH rats will be cultured in vitro and characterized biochemically, metabolically and pharmacologically.